I know this can be very problem-specific -- but it seemed to me the standard approach to train an HMM to recognize a binding pattern of a protein is to use the multiple sequence alignment (MSA), instead of using Baum Welch. I suspect that this is the case because this is what I saw in the current version of HMMer3, which does not provide a baum-welch training procedure for unaligned sequence.

The thing that I saw training with Baum Welch is that once a HMM is trained, using the Viterbi can give a pattern that contains a lot of insertions in the motif, which doesn't make biological sense. This could be mitigated by using Viterbi training, however, I don't see many literature discussing this as a viable approach.

I'd be appreciated if someone could share their experience on training a profile HMM to finding motifs